The present invention relates to a process for preparing bicyclic 1,3-diketones of the formula I, 
where
R1, R2, R3 and R4 are hydrogen, C1-C4-alkyl, C1-C4-alkoxycarbonyl, halogen, cyano, nitro, C1-C4-alkylthio, C1-C4-alkylsulfenyl or C1-C4-alkylsulfonyl and
Z is C1-C4-alkylene, O, S, Nxe2x80x94R5 where
R5=C1-C4-alkyl or C1-C4-alkylcarbonyl,
novel intermediates and novel processes for preparing these intermediates.
Bicyclic 1,3-diketones are useful compounds which can be employed as intermediates in crop protection. U.S. Pat. No. 5,608,101, U.S. Pat. No. 5,536,703, JP 09052807, JP 10265441 and JP 10265415, for example, disclose bicyclooctanediones as intermediates for herbicidally active compounds.
The processes disclosed in JP 10 265 441 and JP 10 256 415 use highly expensive norbornanone as starting material. Owing to the high costs of the starting materials, these processes do not appear to be economical.
Other syntheses have also been described in the literature. They all suffer from the disadvantage that either a large number of synthetic steps are involved (Chem. Ber. 69 (1936), 1199) or that toxicologically and/or ecologically objectionable reagents are used (Can. J. Chem. 42 (1964), 260; Bull. Soc. Chim. Fr. 7-8 (1975), 1691), so that these syntheses are not acceptable from an industrial point of view.
This application is a 371 of PCT/EP01/07639 filed on Jul. 4, 2001.
It is an object of the present invention to provide an alternative process for preparing bicyclic 1,3-diketones of the formula I, which process does not have the disadvantages of the prior art.
We have found that this object is achieved by a process for preparing bicyclic 1,3-diketones of the formula I 
where
R1, R2, R3 and R4 are hydrogen, C1-C4-alkyl, C1-C4-alkoxy-carbonyl, halogen, cyano, nitro, C1-C4-alkylthio, C1-C4-alkylsulfenyl or C1-C4-alkylsulfonyl and
Z is C1-C4-alkylene, O, S, Nxe2x80x94R5 where
R5 is C1-C4-alkyl or C1-C4-alkylcarbonyl,
which comprises
a) reacting a bicyclic olefin of the formula II with haloform in the presence of a base to give the ring-expanded product of the formula III 
xe2x80x83where
R1-R4 and Z are as defined above and
X is halogen;
b) hydrolyzing the allylic halogen of the compound of the formula III to the allyl alcohol of the formula IV 
c) oxidizing the allyl alcohol of the formula IV to the unsaturated ketone of the formula V 
d) reacting the ketone of the formula V with a nucleophilic ion Yxe2x88x92 which stabilizes a negative charge to give the ketone of the formula VI 
e) hydrolyzing the ketone of the formula VI to the bicyclic 1,3-diketone of the formula I.
Furthermore, it has been found that, bypassing the hydrolysis step b), the allylic halogen of the compound of the formula III can be oxidized to the unsaturated ketone of the formula V.
Moreover, it has been found that the reaction of the ketone of the formula V with a nucleophilic ion Yxe2x88x92, which stabilizes a negative charge, to give the ketone of the formula VI can, without intermediate isolation, be hydrolyzed directly to give the bicyclic 1,3-diketone of the formula I.
Furthermore, we have found intermediates of the formula VI 
where
R1, R2, R3 and R4 are hydrogen, C1-C4-alkyl, C1-C4-alkoxy-carbonyl, halogen, cyano, nitro, C1-C4-alkylthio, C1-C4-alkylsulfenyl or C1-C4-alkylsulfonyl and
Z is C1-C4-alkylene, O, S, Nxe2x80x94R5 where
R5 is C1-C4-alkyl or C1-C4-alkylcarbonyl,
Y is cyano, sulfonate, C1-C6-alkylsulfonyl or unsubstituted or C1-C3-alkyl-, C1-C3-alkoxy-, C1-C3-alkylthio-, C1-C3-alkylsulfonyl-, halogen-, cyano-, nitro- or sulfonate-substituted phenylsulfonyl.
Bicyclic 1,3-diketones of the formula I can be present as keto-enol tautomers Ia and Ib. This present invention also relates to a process for preparing tautomers of the formulae Ia and Ib. 
The process according to the invention for preparing compounds I comprises substantially one or more of the process steps a)-e). Also possible are such reaction sequences in which one or more of the process steps a)-e) are combined in one step (one-pot synthesis).
A possible reaction sequence leading to the preparation of the compounds I is compiled in the overview scheme below: 
For the sake of clarity, only the synthesis of one enantiomer is described in each case. The process according to the invention also embraces the synthesis of the other enantiomer in each case.
The individual reaction steps are illustrated in more detail below:
Step a): 
The reaction is carried out, for example, under the following conditions:
This step proceeds via a dihalocarbene, preferably dichlorocarbene, which is generated from haloform and a base.
Haloform, preferably chloroform, is used in the presence of a base, for example an alkali metal hydroxide, an alkaline earth metal hydroxide, an alkali metal alkoxide or an alkali metal amide, preferably NaOH, KOH, sodium methoxide, and, if appropriate, a phase-transfer catalyst, for example tetrabutylammonium chloride, trimethylbenzylammonium chloride or Aliquat 336, in the absence of a solvent or in an inert hydrocarbon or halogenated hydrocarbon, for example hexane, heptane, petroleum ether, dichloromethane, carbon tetrachloride, dichloroethane or chlorobenzene, and, if appropriate, water.
The stoichiometric ratios are, for example, as follows: 1-4 equivalents of haloform, if appropriate 0.0001-0.10 equivalent of phase-transfer catalyst and 1-4 equivalents of base are used per equivalent of the compound II.
The addition is carried out, for example, in the following order: in the inert solvent, compound II and haloform are, if appropriate, admixed with phase-transfer catalyst and, at 0xc2x0 C.-100xc2x0 C., preferably 30-60xc2x0 C., admixed with the base. Work-up is carried out, for example, by stirring the product mixture into water, followed by extraction and, if appropriate, distillation of the resulting residue under reduced pressure. Work-up can also be carried out without purification by distilling off the solvent and using the crude product directly for step b).
The preparation of exo-3,4-dichlorobicyclo[3.2.1]oct-2-ene has already been described in the literature. However, either the yields are unsatisfactory (J. Am. Chem. Soc. 1954, 6162; J. Org. Chem. 28 (1963), 2210; Recl. Trav. Chim. Pays-Bas 80, (1961) 740) or highly toxic phenyltrichloromethylmercury is used (Helv. Chim. Acta 55 (1972), 790; Org. Synth., Coll. Vol V, 1973, 969). The generation of carbene from ethyl trichloroacetate and base (Org. Synth. Coll. Vol. VI, 1988, 142) is highly exothermic: when this synthesis procedure was repeated, there was product outflow from the apparatus. carbene addition under phase-transfer catalysis is likewise already known in the literature (Houben/Weyl, Methoden der organischen Chemie [Methods of organic chemistry], Vol. E19/b, 1989, 1527, Thieme Verlag, Stuttgart; Synthesis 9 (1972), 485). However, there is still scope for improvement with respect to yield and reaction time. When these procedures were checked, the yields obtained for larger batches were considerably lower. It has been observed that dichlorocarbene reacts with water to give carbon monoxide which, on an industrial scale, represents a potential danger.
Step b): 
The hydrolysis is carried out, for example, under the following conditions: suitable solvents are water, with or without addition of a phase-transfer catalyst, tetrahydrofuran, dimethylformamide or dimethyl sulfoxide. The hydrolysis is carried out, for example, using alkali metal hydroxides, such as sodium hydroxide or potassium hydroxide, or alkaline earth metal hydroxides, for example magnesium hydroxide or calcium hydroxide; preference is given to NaOH and KOH.
The reaction is carried out at from 0xc2x0 C. to the boiling point of the solvent, preferably at from room temperature to the reflux temperature of the solvent in question. The stoichiometric ratios are as follows: 1-5 equivalents of base, preferably 1-1.5 equivalents of base, are used per equivalent of the compound III.
Work-up is carried out, for example, by stirring the mixture into water and extracting with an organic solvent and subsequent fractional distillation. If the solvent used is water, extraction can be carried out directly.
The hydrolysis of a cyclic halogen atom has already been described (J. Chem. Soc. Perk. Trans. II, 1982, 39). However, the fact that this reaction takes a very long time (3 days) makes its use unattractive for an industrial synthesis. In another literature reference (Synth. Comm. 24 (1994), 2923), formic acid and selenium dioxide are used to synthesis the compounds IV. However, the high toxicity of selenium compounds excludes this variant, too, from being used in an industrial preparation.
Step c): 
The oxidation can be carried out, for example, using the following oxidizing agents: air, manganese dioxide, potassium permanganate, Jones""s reagent (chromic acid/sulfuric acid), dimethyl sulfoxide, if appropriate with additives, such as NaHCO3, potassium hydrogenphosphate or potassium dihydrogenphosphate, or activators, such as oxalyl chloride, phosphorus trichloride, phosphorus oxychloride, thionyl chloride, acetyl chloride, acetic anhydride, sulfur trioxide/pyridine complex, tertiary amine oxides, for example trimethylamine oxide or N-methylmorpholine N-oxide, hydrogen peroxide, if appropriate using a catalyst, for example sodium tungstate, sodium hypochlorite, peracids, for example perbenzoic acids, peracetic acid or pertrifluoroacetic acid, bromine, chlorine, ruthenium tetraoxide, if appropriate catalytically with auxiliary oxidants, for example NaIO4, pyridinium dichromate, pyridinium chlorochromate, cerium ammonium nitrate, nitric acid, lead tetraacetate, N-chlorosuccinimide, N-bromosuccinimide, preferably sodium hypochlorite, hydrogen peroxide, if appropriate in the presence of a catalyst, for example sodium tungstate, air, N-chlorosuccinimide or dimethyl sulfoxide with additives, for example potassium hydrogenphosphate/potassium dihydrogenphosphate, or activators, for example oxalyl chloride, thionyl chloride, acetic anhydride or phosphorus trichloride. Suitable solvents are water, inert hydrocarbons, such as hexane, heptane or petroleum ether, or inert chlorinated hydrocarbons, such as dichloromethane or chlorobenzene. If the oxidation agent is a liquid, the use of additional solvents can be dispensed with.
The oxidation is carried out, for example, at from xe2x88x9260xc2x0 C. to the boiling point of the solvent in question.
In the literature, the synthesis of compounds V from alkoxynorbornenes (Bull. Soc. Chim. Fr. 7-8 (1974), 1638) is described. The only easy way to obtain alkoxynorbornenes is from norbornanone and, owing to the high price of norbornanone, this route is not of any interest for an industrial synthesis.
Combination of Steps b) and c): 
It is also possible to oxidize the allyl chloride III directly to the ketone of the formula V, bypassing step b). Oxidizing agents suitable for this purpose are, for example, air, dimethyl sulfoxide in the presence of additives, for example bases such as sodium bicarbonate or potassium hydrogenphosphate and potassium dihydrogenphosphate, tertiary amine oxides, for example 4-dimethylaminopyridine N-oxide or trimethylamine N-oxide, in inert hydrocarbons, such as hexane, heptane or petroleum ether, or without addition of solvent.
Step d): 
The reaction is carried out, for example, under the following conditions: the solvents used are, for example: polar aprotic solvents, such as dimethylformamide, dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, dimethylpropyleneurea, acetonitrile or propionitrile, polar protic solvents, such as methanol, ethanol, n-propanol, isopropanol or water, if appropriate with addition of a phase-transfer catalyst, ethers, such as diethyl ether, dibutyl ether, diisopropyl ether, tetrahydrofuran, dioxane or methyl tert-butyl ether, halogenated hydrocarbons, such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane or chlorobenzene, aromatic compounds, such as benzene, toluene, xylene or nitrobenzene, ketones, such as acetone, butanone or methyl isobutyl ketone, or carboxylic esters, such as ethyl acetate. Preference is given to using, as solvents, alcohols, acetonitrile, dichloromethane and acetone. The reaction is carried out at from xe2x88x9240xc2x0 C. to 150xc2x0 C., preferably at from room temperature to the reflux temperature of the solvent in question. Suitable nucleophilic ions which stabilize a negative charge are, eg, cyanides, sulfites, C1-C6-alkylsulfinates or unsubstituted or C1-C3-alkyl-, C1-C3-alkoxy-, C1-C3-alkylthio-, C1-C3-alkylsulfonyl-, halogen-, cyano-, nitro- or sulfonate-substituted phenylsulfinate and mixtures thereof. Sources of cyanide can be, for example, hydrocyanic acid, alkali metal cyanides, such as lithium cyanide, sodium cyanide or potassium cyanide, or organic compounds, trimethylsilyl cyanide or acetone cyanohydrin. Useful sources of sulfite are, for example, sulfurous acid, alkali metal sulfites, such as sodium sulfite or potassium sulfite, or alkali metal hydrogensulfites, for example sodium hydrogensulfite. Useful sulfinates are alkylsulfinates, such as sodium methylsulfinate, or arylsulfinates, such as sodium tolylsulfinate.
Suitable bases are, for example, nitrogen bases, such as triethylamine, pyridine, diazabicycloundecane (DBU) or dimethylaminopyridine (DMAP), alkali metal hydroxides, such as lithium hydroxide, sodium hydroxide or potassium hydroxide, alkaline earth metal hydroxides, such as barium hydroxide or calcium hydroxide, alkali metal carbonates, such as sodium carbonate or potassium carbonate, alkali metal bicarbonates, such as sodium bicarbonate or potassium bicarbonate, or alkali metal acetates, such as sodium acetate or potassium acetate.
The stoichiometric ratios are as follows: 1-5 equivalents of the nucleophilic ion which stabilizes a negative charge, preferably 1-2 equivalents, and, if appropriate, 1-5 equivalents of base, preferably 1-3 equivalents, are used per equivalent of the compound V. In certain cases, it may also be advantageous to use a catalytic amount of the nucleophilic ion which stabilizes a negative charge of 0.0001-10 mol %, preferably of 0,001-5 mol %. Work-up is carried out, for example, according to the following scheme: a) addition of water and extraction with an organic solvent, b) solvent exchange by distillative removal of the solvent, c) no purification; the solution is used directly in the next step.
This reaction is a process for converting a 2-halo alk-2-en-1-one into a 3-cyano alk-2-en-1-one, for example, if the nucleophilic ion Yxe2x88x92 which stabilizes a negative charge is the cyano group. However, Yxe2x88x92 may also be alkylsulfinate, arylsulfinate or sulfite. Reactions of 2-bromocycloalk-2-en-1-ones with NaCN or KCN are known from Tetrahedron Lett. 28 (1987), 6485-6488; Tetrahedron 43 (1987), 5593-5604.
Step e): 
The reaction is carried out, for example, under the following conditions: suitable solvents are, for example, alcohols, such as methanol, ethanol, propanol or isopropanol, water, acetonitrile, dioxane or tetrahydrofuran, preferably methanol, ethanol and water. The hydrolysis can be initiated, for example, by alkali metal hydroxides, such as lithium hydroxide, sodium hydroxide or potassium hydroxide, alkaline earth metal hydroxides, such as calcium hydroxide or barium hydroxide, aluminum hydroxide, alkali metal carbonates, such as sodium carbonate or potassium carbonate, alkali metal bicarbonates, such as sodium bicarbonate or potassium bicarbonate, acetates, such as sodium acetate or potassium acetate, and nitrogen bases, such as triethylamine, pyridine or ammonia dissolved in water. However, it may also be advantageous to carry out the hydrolysis in acidic medium. Suitable acids are, for example, inorganic acids, for example hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, perchloric acid, chloric acid, hydrobromic acid and/or hydriodic acid, or organic acids, for example formic acid, acetic acid, propionic acid, butyric acid, stearic acid, oleic acid, benzoic acids and phenols. The reaction can be carried out at from xe2x88x9240xc2x0 C. to 150xc2x0 C., preferably at from room temperature to the reflux temperature of the solvent in question. The stoichiometric ratios are, for example, 1-5 equivalents, preferably 1-2 equivalents, of acid or base per equivalent of the compound VI.
Steps d) and e) can also be carried out as a one-pot reaction, using the reagent quantities stated in each case.
Compounds of the Formula VI
where
X [sic] is cyano, sulfonate, C1-C6-alkylsulfonyl or unsubstituted or C1-C3-alkyl-, C1-C3-alkoxy-, C1-C3-alkylthio-, C1-C3-alkylsulfonyl-, halogen-, cyano-, nitro- or sulfonate-substituted phenylsulfonyl
are novel.